1. Field of the Invention
The present invention relates to an apparatus and a method wherein a sample is cut with a blade having a metal thin film on the surface at least in part, and the slice of the sample adhering to the blade surface is subjected to mass spectrometry.
2. Description of the Related Art
The importance of analysis of proteins as gene products existing in vivo is rapidly coming to the fore with progress in genome analysis in recent years. Particularly, the importance of protein analysis in tissue slices is pointed out. For example, many attempts have been made to elucidate proteins associated with recurrence or metastasis from cancer tissue slices. Protein analysis approaches with biological samples are generally performed according to the following procedures:    (1) extraction of proteins from biological tissues or cells;    (2) separation of the proteins from the extracts (solutions);    (3) analysis of the separated proteins or (poly)peptides as degradation products thereof; and    (4) identification of the obtained analysis result.
While a variety of protein analysis methods are known, time-of-flight mass spectrometry has received attention as a method capable of accurately analyzing trace amounts of samples. The pamphlet of International Publication of WO2005/003715 discusses an information acquisition method and apparatus based on TOF-SIMS (time-of-flight secondary ion mass spectrometry), which are directed to visualizing the two-dimensional distribution of proteins in biological tissue slices. In this analysis method, a substance for promoting ionization and/or a digestive enzyme are directly added to biological tissue slices, and information about a protein type (including information about peptides resulting from partial hydrolysis by the digestive enzyme) is visualized by TOF-SIMS with the positional information thereof being held. Thus, this analysis method is not intended to immediately analyze the section of the cut biological tissue.
Japanese Patent Application Laid-Open No. 2004-219261 (corresponding to U.S. Patent Application Publication No. US-2004-0232330) discusses an approach, which involves analyzing, by mass spectrometry, a section of a multilayered thin film cut obliquely with a microtome and consequently analyzing the thin film with a high spatial resolution. On the other hand, Analytical Chemistry, 74 (2002), 4955-4968, “Organic secondary ion mass spectrometry: sensitivity enhancement by gold deposition” discusses a technique for improving the ionization efficiency of TOF-SIMS by gold deposition. A gold substrate is also known to produce ion sensitizing effect, even in the presence of a sample thereon, if the sample is thin to such an extent that the influence of an ion beam reaches the substrate.
Thus, if a slice of a sample cut with a microtome or SAICAS (surface and interfacial cutting analysis system) is transferred onto a metal substrate and subjected to mass spectrometry, molecules existing in the slice of the sample are efficiently ionized by the ion sensitizing effect. Therefore, improvement in sensitivity can be expected. However, the slice of the sample is not easy to transfer onto the substrate with good positional accuracy.
As discussed in Japanese Patent Application Laid-Open No. 2004-219261, the cut surface of a sample on a substrate is easily analyzed. However, the acquisition of ion sensitizing effect requires depositing a metal onto the section of the sample on the substrate after sample cutting. As a result, the metal is deposited even onto a portion in no need of deposition in the sample unless the portion is masked. One run of mass spectrometry on the sample surface on the substrate results in the degradation and volatilization of tissue degradation products within the sample due to high energy irradiation. Thus, the sample analyzed once on the substrate has morphological changes in both the surface and interior thereof caused by metal deposition and analysis. Such a sample had the problem of not serving as a proper analyte for obtaining additional information on the interior thereof.